The midget and parasol ganglion cells are the most abundant output neurons in the primate retina, and are fundamental for our perception of color, form and motion. Midget (sustained) ganglion cells respond optimally to slow changes in light intensity, whereas parasol (transient) ganglion cells can detect more rapid fluctuations, a feature that enhances sensitivity to motion. The objective of this study is to determine how the various types of bipolar cells, the second- order neurons, process cone signals to generate these distinct temporal response properties. Since few functional recordings have been made from primate cone bipolar cells, the mechanisms that mediate temporal tuning remain unclear. Moreover, our preliminary data indicate that previously proposed models for temporal tuning, from work in lower-order mammals, may not directly apply to primates. In preliminary studies, we have found that, unlike other mammals, all macaque OFF cone bipolar cells receive input primarily through kainate- type glutamate receptors. In Aim 1, we will test the hypothesis that heterogeneity in kainate receptor subunit composition, and kainate receptor auxiliary proteins, shapes the temporal response properties of OFF bipolar cells. In Aim 2, we will test the hypothesis that selective expression of voltage-gated channels tunes specific OFF cone bipolar cell types to higher temporal frequencies. In Aim 3, we will determine whether a newly identified OFF bipolar cell type makes input to OFF parasol cells, and will test whether there are eccentricity-dependent changes in OFF midget ganglion cell circuitry. We will address these aims using a combination of immunohistochemistry, confocal and super-resolution microscopy, and patch-clamp electrophysiology. These studies will provide new insights into the functional mechanisms of temporal processing in the primate retina, and should also reveal new details regarding the circuitry of midget and parasol ganglion cells. Thus, this proposal addresses two explicit needs identified by the National Eye Institute which are; 1) to understand the structure, function and circuitry of retinal neurons and 2) to decode the electrical patterns used by retina neurons to transmit visual information. The macaque is an ideal model system for the human retina, and thus the results of this study will be invaluable for developing methods to restore or treat vision loss from retinal disease, and for interpreting tests of visual function.